Alzheimer's disease (AD) is multi-dimensional in nature, characterized not only by cognitive and functional decline, but neuropsychiatric symptoms that develop commonly and are associated with considerable morbidity. These include agitation and psychosis, which often co-occur and have a particularly high persistence rate. The trial proposes a novel design to address whether emergence of agitation and/or psychosis can be delayed by agents that have psychotropic as well as possible neuroprotective properties. We proposed a randomized, placebo- controlled, double blind, multicenter, two-year trial of low-dose (500 mg/d) valproate therapy in 300 outpatients with mild to moderate AD who lack agitation and psychosis at baseline. Subjects will be followed on a regular basis with clinic visits as well as telephone contacts, providing assessments of behavior, cognition, function, safety and tolerability. Valproate was selected because of its possibly symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to patients with AD who lack agitation and psychosis at baseline will delay the emergence of agitation and/or psychosis. An effect of this nature may have significant public health implications, for instance, by delaying institutionalization. Secondary hypotheses will be addressed as well. One is that chronic valproate administration to patients with AD will attenuate clinical progression of illness measured by reduced rate of cognitive or functional decline. In addition. Issues related to safety and tolerability with chronic low-dose therapy will be addressed. Biological specimens will be obtained to study markers selected for their relevance to the disease as well as the postulated mechanism of action of the therapy. After the double-blind phase, there will be a two-month single-blind placebo-controlled washout phase to address possible emergence of psychopathology that previously might have been suppressed by active therapy.